Saturday, August 9, 2014

Eosinophils preference for peanut can lead to allergy

Peanut allergy is a very
serious medical condition. Usually, gut immune system tolerates
antigens derived from orally consumed food. In rare situations,
however, immune system mistakes food antigens for noxious stimuli and mounts
exaggerating IgE response. IgE response is basically a highly skewed
Th2 response. No one knows how or why it happens.

I am going to review one
paper published in Journal of Experimental Medicine (JEM) that
studied animal model of peanut allergy (1). I would like to point out
here that this mouse model of peanut allergy is an experimental model
and may not fully or even partially recapitulate the mechanism of
initiation of peanut allergy in humans.

First, analysis of gut
lymphoid tissue showed that small intestine contained higher
percentage of eosinophils (~ 20%). Interestingly, there was inverse
relationship between number of eosinophils and level of gut
microbiome.

Third, the authors found
that IL-4 secretion by eosinophils was not necessary to induce peanut
allergy in this model.

Fourth, it turned out
that gut CD11c+ /CD103+ dendritic cells were also required to induce
peanut allergy in this model since it was abolished in CD11c-DTR bone
marrow chimera mice upon DT (diphtheria toxin) application.

Incubation of mouse
BMDCs or human in vitro derived DCs with native EPO, but not
heat-inactivated EPO, induced their activation and IL-6 secretion
without compromising their viability.

To confirm that EPO
played a role in mouse model of peanut allergy, the authors tested
EPO-deficient mice. As shown below, EPO-deficient mice failed to
generate peanut specific IgE response similar to eosinophil-deficient
GATA1 mutant mice.

In summary, the authors
proposed that mechanism of peanut sensitization as following: food
peanut antigen activates gut eosinophils to release EPO to drive
local DCs migration into local LN to prime Th2 response.

Some consideration: (1)
do eosinophils sense peanut? The authors do not show if peanut alone
can activate eosinophils. (2) while data from EPO-deficient mice is
impressive, the authors did not explain whether EPO-deficient mice
selectively lacks EPO in eosinophils as the name would suggest (BM
chimera would have been a good experiment).